The overall aims of this project are to develop and implement novel methods for quantitative characterization of tissue by magnetic resonance imaging (MRI). The microscopic compartition of water in tissues reflects potentially important structural properties that may be probed by diverse MRI measurements. In particular, water diffusion and nuclear magnetic resonance (NMR) relaxation cannot be described by single components in many tissues. With some success, multiple component characterization of these attributes has been proposed and studied in an attempt to extract specific information about the micro-anatomical water compartments from which they are derived. The further development and application of novel, effective methods for acquiring and analyzing sub-voxel characteristics promises to be useful for assessing structure and pathophysiology in various tissues, particularly nerve and muscle. The studies proposed herein will develop new methods for such studies and provide a more complete understanding of the biological basis of MRI contrast in white matter and muscle, in normal and pathological conditions. Experimental studies on model tissues will establish comprehensive and quantitative in vivo descriptions of water diffusion, longitudinal and transverse relaxation, and magnetization transfer, and how they correlate to each other and the physical compartments from which they are derived. These observations can then be used to design novel MRI methods, which are more specific for depicting tissue microstructure. One example, amongst others, is the aim to develop efficient and effective MRI methods of visualizing and quantifying myelin content in the brain based on detailed compartmental models of white matter. PUBLIC HEALTH RELEVANCE: MRI is a widespread diagnostic imaging modality capable of relatively non-invasive visualization of soft tissue. The contrast in MRI results from many complex interactions of water molecules in the body with each other and the physical and chemical characteristics of their local environments. This research program aims to better relate MRI contrast to specific micro-anatomical characteristics in neural tissue and skeletal muscle. This work has broad potential impact the diagnostic and prognostic capabilities of MRI for a wide array of diseases and injuries.